Research Update Corner: Spring 2011

The Lustgarten Foundation helped support Dr. Bert Vogelstein, The Johns Hopkins Kimmel Cancer Center, and his team to sequence the genome of pancreatic cancers. At the time of its completion in 2008, the pancreatic cancer genome project* represented the most complete genetic analysis of any tumor type. The project has laid the groundwork for new areas of pancreatic cancer investigation, serving as a steppingstone for additional studies in promising new directions. In this issue of Research Update Corner, we will focus on three exciting new studies that are shaping the way researchers look at the development, diagnosis and detection of the disease. The studies build on insights gained from the landmark pancreatic cancer genome project.

In October 2010, news broke in the prestigious journal Nature by Dr. Shinichi Yachida and colleagues in the laboratory of Dr. Christine Iacobuzio-Donahue of Johns Hopkins University describing that pancreatic cancer develops much more slowly than scientists thought.This discovery contradicts an existing idea that pancreatic cancers spread early in their development. Rather, Dr. Iacobuzio and colleagues found that it takes at least a decade from the first cancer-causing mutation in a normal pancreas cell, until the development of a full-blown cancer cell. It takes another five to seven years before this initial cancer cell turns into a tumor, detectable through traditional imaging methods. In other words, pancreatic cancer takes more than a decade to develop, and up to another seven years to spread. This pivotal discovery offers critical insights to researchers, defining a window of opportunity in which to detect pancreatic cancer early, when the chances for a cure are greatest.

Nevertheless, to take advantage of this exciting information, scientists need powerful research tools that can detect early mutations in pancreas cells. In addition, they need to better understand the processes that cause normal cells to start down the long road to going “bad.” Dr. Qing Wang and colleagues in the laboratory of Dr. Vogelstein recently reported in the journal Proceedings of the National Academy of Sciences (PNAS) that changes in DNA (mutations) can be detected in proteins. We know from the pancreatic cancer genome project that nearly all pancreatic cancers have a K-ras gene DNA mutation, making this gene an ideal target for early detection.

Dr. Vogelstein used the cutting edge SRM technology to see these mutations in proteins. A previous installment of RUC explained how pancreatic cancer is currently understood and treated based on what we see about it, and how biomarkers can be used to detect the presence of cancer before it is visible under a microscope and through current imaging technologies. Although Dr. Vogelstein’snovel use of SRM technology is not ready for use in the clinic, it holds exciting potential for using protein biomarkers in the early detection of pancreatic cancer. Today, with support from The Lustgarten Foundation, Dr. Vogelstein and his team are actively working to optimize SRM technology for use in blood and cystic fluids.

Another exciting study published inScience by Dr. David Ting and colleagues in the laboratory of Dr. Daniel Haber of Massachusetts General Hospital (MGH) Cancer Center has revealed a previously unknown role of small snipets of DNA known as “satellite repeats.” You may know that human DNA contains genes, but what is less known is that only approximately 2% of our DNA codes for genes; the rest is unknown—a “big black box” of the human genome.

Until now, satellite repeats have been thought to be a largely inactive part of the genome, a sort of “junk” in the black box. Drs. Ting and Haber studied pancreatic cancer, and discovered that satellite repeats become active as the disease develops. In fact, satellite repeats become progressively more active as pancreatic cancer moves from early to later stages. Further, they are not active in normal tissue. The findings may offer a novel cancer biomarker for pancreatic cancer, and together, these three studies and hold exciting promise for early detection of the disease.

Now in phase 2, The Lustgarten Foundation’s Biomarker Development Project will validate the antibodies deemed predictive of early pancreatic cancer lesions. This large-scale validation phase will be conducted by PCRC member institution Dana-Farber Cancer Institute/Harvard Medical School, in cooperation with University of California at San Francisco and Fred Hutchinson Cancer Research Center.

*The pancreatic cancer genome project was made possible with major funding from The Sol Goldman Charitable Trust and The Lillian Goldman Charitable Trust, and significant funding from The Lustgarten Foundation.